Modular, Scalable Synthesis of Group A Streptogramin Antibiotics.

Abstract

Streptogramin antibiotics are used clinically to treat multidrug-resistant bacterial infections, but their poor physicochemical properties and narrow spectra of activity have limited their utility. New methods to chemically modify streptogramins would enable structural optimization to overcome these limitations as well as to combat growing resistance to the class. Here we report a modular, scalable synthesis of group A streptogramin antibiotics that proceeds in 6-8 linear steps from simple chemical building blocks. We have applied our route to the synthesis of four natural products in this class including two that have never before been accessed by fully synthetic routes. We anticipate that this work will lead to the discovery of new streptogramin antibiotics that overcome previous limitations of the class.